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according to investigators.
Two recent studies presented at the American Thoracic Society’s international conference demonstrated the benefits of glucocorticoid therapy among patients with mild persistent or intermittent asthma while highlighting differential responses to steroids among patients with high versus low levels of eosinophils in sputum. Both studies were simultaneously published in the New England Journal of Medicine.
The first study, SIENA, led by Stephen C. Lazarus, MD of the University of California, San Francisco, and colleagues, involved 295 patients with mild, persistent asthma. Patients were classified as having either a high or low level of eosinophils in sputum, with a low level defined by two sputum samples consisting of less than 2% eosinophils. After a single-blind placebo run-in period of 6 weeks, patients were randomized to receive either mometasone (an inhaled glucocorticoid), tiotropium (a long-acting muscarinic antagonist [LAMA]), or placebo for 12 weeks each, with subsequent crossover through the two remaining treatments. The primary outcome was the response to each active agent, compared with placebo among low-eosinophil patients who had a differential response to a trial agent.
Out of 295 patients, 221 (75%) had low eosinophils and 74 (25%) had high eosinophils. In the low-eosinophil subgroup, 59% of patients had a differential response to a trial agent; among these, 57% responded better to mometasone, compared with 43% who responded better to placebo, and 60% responded better to tiotropium, compared with 40% who responded better to placebo.
Turning to secondary analyses, among patients with high eosinophil levels who had a differential response, 74% responded better to mometasone, compared with 26% who responded better to placebo, and 57% responded better to tiotropium, compared with 43% who responded better to placebo.
In an additional exploratory analysis, adults with low eosinophil levels had better responses to tiotropium than placebo (62% vs 38%).
The researchers stated that a key finding of the study is that three-quarters of the mild, persistent asthma population had low eosinophil levels, far fewer than expected and that the difference in their response to mometasone compared to tiotropium was not significant.
“Our results raise the question of whether treatment guidelines should be reevaluated for patients with mild, persistent asthma for whom evidence of type 2 inflammation is lacking,” the investigators wrote. “The need for a change in treatment strategy is further highlighted by a growing body of literature suggesting that mild, persistent asthma can be managed safely without the daily use of inhaled glucocorticoids and by data showing that patients with a low eosinophil level may not have a favorable response to inhaled glucocorticoids” (New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1814917).
The second study, Novel START, conducted by lead author Richard Beasley, DSc, of the Medical Research Institute of New Zealand, Wellington, and colleagues, compared the efficacy of two inhaled glucocorticoid regimens and albuterol alone for patients with mild persistent or intermittent asthma, measured by annualized exacerbation rate.
Initial randomization involved 675 patients, of whom 668 were included in the final analysis. Patients were randomized into three groups: albuterol as needed (100 mcg, two inhalations as needed for asthma symptoms), budesonide maintenance (200 mcg, one inhalation twice daily with as-needed albuterol), or budesonide/formoterol (budesonide 200 mcg and formoterol 6 mcg, one inhalation as needed). Along with annualized exacerbation rate, several secondary outcomes assessed symptoms, respiratory function, and number of severe exacerbations.
Data analysis showed that patients in the budesonide groups had similar rates of annualized exacerbation, both of which were significantly better than the exacerbation rate in the albuterol-only group; the absolute rate of exacerbations per patient per year was 0.175, 0.195, and 0.400 for budesonide maintenance, budesonide/formoterol, and albuterol only, respectively. Similarly, the median fraction of exhaled nitric oxide (FENO) was lower in the budesonide groups than in the albuterol-only group. Patients in the budesonide/formoterol group had a 56% lower relative risk of severe pulmonary exacerbation than patients in the budesonide maintenance group and a 60% lower relative risk than the albuterol group. However, maintenance budesonide provided better symptom relief than budesonide/formoterol, “which suggests that for the patient for whom asthma symptoms rather than exacerbations are the most bothersome, maintenance treatment has value,” the investigators wrote (New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1901963).
“The findings of our trial are consistent with evidence regarding the treatment of moderate and severe asthma – that maintenance and reliever therapy” with inhaled glucocorticoid/formoterol “results in a lower risk of severe exacerbations than maintenance therapy with an inhaled glucocorticoid–[long-acting beta agonist] and as-needed SABA,” the investigators concluded.
SIENA was funded by National Heart, Lung, and Blood Institute, with medications provided by Boehringer Ingelheim, Merck, and Teva; the investigators reported relationships with Sanofi, Vectura, Circassia, DBV Technologies, and others. Novel START was funded by AstraZeneca and the Health Research Council of New Zealand; the investigators reported relationships with GlaxoSmithKline, Genentech, Theravance Biopharma, and others.
SOURCES: Beasley et al. New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1901963; Lazarus et al. New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1814917.
Gary W. K. Wong, MD, commented in an editorial accompanying the two studies, “Approximately 1 year ago, the SYGMA 1 and SYGMA 2 trials, involving patients with mild persistent asthma, suggested that as-needed use of a budesonide–formoterol combination was as effective as budesonide maintenance therapy in the prevention of exacerbations, with the added benefit of decreased overall glucocorticoid exposure; however, it remained unknown if this strategy was appropriate for patients with mild intermittent asthma and among patients lacking eosinophilic inflammation. The two reported studies attempt to address these knowledge gaps.”
He noted that both trials showed that “patients with mild asthma whose only asthma treatment was a SABA [short-acting beta2-agonists] as needed for relief of asthma symptoms were at considerable risk for exacerbations. Replacement of as-needed SABA treatment with as-needed budesonide/formoterol or inhaled glucocorticoid maintenance therapy could reduce such risk by approximately 50%. When considering maintenance therapy for persistent asthma, one must be aware that not all types of airway inflammation respond equally well to inhaled glucocorticoid therapy.”
Gary W.K. Wong, MD, is a professor in the department of pediatrics at Prince of Wales Hospital, Chinese University of Hong Kong. He made his remarks in an editorial in the New England Journal of Medicine (2019 May 19. doi: 10.1056/NEJMe1905354). Dr. Wong disclosed that he has no relevant financial conflicts of interest.
Gary W. K. Wong, MD, commented in an editorial accompanying the two studies, “Approximately 1 year ago, the SYGMA 1 and SYGMA 2 trials, involving patients with mild persistent asthma, suggested that as-needed use of a budesonide–formoterol combination was as effective as budesonide maintenance therapy in the prevention of exacerbations, with the added benefit of decreased overall glucocorticoid exposure; however, it remained unknown if this strategy was appropriate for patients with mild intermittent asthma and among patients lacking eosinophilic inflammation. The two reported studies attempt to address these knowledge gaps.”
He noted that both trials showed that “patients with mild asthma whose only asthma treatment was a SABA [short-acting beta2-agonists] as needed for relief of asthma symptoms were at considerable risk for exacerbations. Replacement of as-needed SABA treatment with as-needed budesonide/formoterol or inhaled glucocorticoid maintenance therapy could reduce such risk by approximately 50%. When considering maintenance therapy for persistent asthma, one must be aware that not all types of airway inflammation respond equally well to inhaled glucocorticoid therapy.”
Gary W.K. Wong, MD, is a professor in the department of pediatrics at Prince of Wales Hospital, Chinese University of Hong Kong. He made his remarks in an editorial in the New England Journal of Medicine (2019 May 19. doi: 10.1056/NEJMe1905354). Dr. Wong disclosed that he has no relevant financial conflicts of interest.
Gary W. K. Wong, MD, commented in an editorial accompanying the two studies, “Approximately 1 year ago, the SYGMA 1 and SYGMA 2 trials, involving patients with mild persistent asthma, suggested that as-needed use of a budesonide–formoterol combination was as effective as budesonide maintenance therapy in the prevention of exacerbations, with the added benefit of decreased overall glucocorticoid exposure; however, it remained unknown if this strategy was appropriate for patients with mild intermittent asthma and among patients lacking eosinophilic inflammation. The two reported studies attempt to address these knowledge gaps.”
He noted that both trials showed that “patients with mild asthma whose only asthma treatment was a SABA [short-acting beta2-agonists] as needed for relief of asthma symptoms were at considerable risk for exacerbations. Replacement of as-needed SABA treatment with as-needed budesonide/formoterol or inhaled glucocorticoid maintenance therapy could reduce such risk by approximately 50%. When considering maintenance therapy for persistent asthma, one must be aware that not all types of airway inflammation respond equally well to inhaled glucocorticoid therapy.”
Gary W.K. Wong, MD, is a professor in the department of pediatrics at Prince of Wales Hospital, Chinese University of Hong Kong. He made his remarks in an editorial in the New England Journal of Medicine (2019 May 19. doi: 10.1056/NEJMe1905354). Dr. Wong disclosed that he has no relevant financial conflicts of interest.
according to investigators.
Two recent studies presented at the American Thoracic Society’s international conference demonstrated the benefits of glucocorticoid therapy among patients with mild persistent or intermittent asthma while highlighting differential responses to steroids among patients with high versus low levels of eosinophils in sputum. Both studies were simultaneously published in the New England Journal of Medicine.
The first study, SIENA, led by Stephen C. Lazarus, MD of the University of California, San Francisco, and colleagues, involved 295 patients with mild, persistent asthma. Patients were classified as having either a high or low level of eosinophils in sputum, with a low level defined by two sputum samples consisting of less than 2% eosinophils. After a single-blind placebo run-in period of 6 weeks, patients were randomized to receive either mometasone (an inhaled glucocorticoid), tiotropium (a long-acting muscarinic antagonist [LAMA]), or placebo for 12 weeks each, with subsequent crossover through the two remaining treatments. The primary outcome was the response to each active agent, compared with placebo among low-eosinophil patients who had a differential response to a trial agent.
Out of 295 patients, 221 (75%) had low eosinophils and 74 (25%) had high eosinophils. In the low-eosinophil subgroup, 59% of patients had a differential response to a trial agent; among these, 57% responded better to mometasone, compared with 43% who responded better to placebo, and 60% responded better to tiotropium, compared with 40% who responded better to placebo.
Turning to secondary analyses, among patients with high eosinophil levels who had a differential response, 74% responded better to mometasone, compared with 26% who responded better to placebo, and 57% responded better to tiotropium, compared with 43% who responded better to placebo.
In an additional exploratory analysis, adults with low eosinophil levels had better responses to tiotropium than placebo (62% vs 38%).
The researchers stated that a key finding of the study is that three-quarters of the mild, persistent asthma population had low eosinophil levels, far fewer than expected and that the difference in their response to mometasone compared to tiotropium was not significant.
“Our results raise the question of whether treatment guidelines should be reevaluated for patients with mild, persistent asthma for whom evidence of type 2 inflammation is lacking,” the investigators wrote. “The need for a change in treatment strategy is further highlighted by a growing body of literature suggesting that mild, persistent asthma can be managed safely without the daily use of inhaled glucocorticoids and by data showing that patients with a low eosinophil level may not have a favorable response to inhaled glucocorticoids” (New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1814917).
The second study, Novel START, conducted by lead author Richard Beasley, DSc, of the Medical Research Institute of New Zealand, Wellington, and colleagues, compared the efficacy of two inhaled glucocorticoid regimens and albuterol alone for patients with mild persistent or intermittent asthma, measured by annualized exacerbation rate.
Initial randomization involved 675 patients, of whom 668 were included in the final analysis. Patients were randomized into three groups: albuterol as needed (100 mcg, two inhalations as needed for asthma symptoms), budesonide maintenance (200 mcg, one inhalation twice daily with as-needed albuterol), or budesonide/formoterol (budesonide 200 mcg and formoterol 6 mcg, one inhalation as needed). Along with annualized exacerbation rate, several secondary outcomes assessed symptoms, respiratory function, and number of severe exacerbations.
Data analysis showed that patients in the budesonide groups had similar rates of annualized exacerbation, both of which were significantly better than the exacerbation rate in the albuterol-only group; the absolute rate of exacerbations per patient per year was 0.175, 0.195, and 0.400 for budesonide maintenance, budesonide/formoterol, and albuterol only, respectively. Similarly, the median fraction of exhaled nitric oxide (FENO) was lower in the budesonide groups than in the albuterol-only group. Patients in the budesonide/formoterol group had a 56% lower relative risk of severe pulmonary exacerbation than patients in the budesonide maintenance group and a 60% lower relative risk than the albuterol group. However, maintenance budesonide provided better symptom relief than budesonide/formoterol, “which suggests that for the patient for whom asthma symptoms rather than exacerbations are the most bothersome, maintenance treatment has value,” the investigators wrote (New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1901963).
“The findings of our trial are consistent with evidence regarding the treatment of moderate and severe asthma – that maintenance and reliever therapy” with inhaled glucocorticoid/formoterol “results in a lower risk of severe exacerbations than maintenance therapy with an inhaled glucocorticoid–[long-acting beta agonist] and as-needed SABA,” the investigators concluded.
SIENA was funded by National Heart, Lung, and Blood Institute, with medications provided by Boehringer Ingelheim, Merck, and Teva; the investigators reported relationships with Sanofi, Vectura, Circassia, DBV Technologies, and others. Novel START was funded by AstraZeneca and the Health Research Council of New Zealand; the investigators reported relationships with GlaxoSmithKline, Genentech, Theravance Biopharma, and others.
SOURCES: Beasley et al. New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1901963; Lazarus et al. New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1814917.
according to investigators.
Two recent studies presented at the American Thoracic Society’s international conference demonstrated the benefits of glucocorticoid therapy among patients with mild persistent or intermittent asthma while highlighting differential responses to steroids among patients with high versus low levels of eosinophils in sputum. Both studies were simultaneously published in the New England Journal of Medicine.
The first study, SIENA, led by Stephen C. Lazarus, MD of the University of California, San Francisco, and colleagues, involved 295 patients with mild, persistent asthma. Patients were classified as having either a high or low level of eosinophils in sputum, with a low level defined by two sputum samples consisting of less than 2% eosinophils. After a single-blind placebo run-in period of 6 weeks, patients were randomized to receive either mometasone (an inhaled glucocorticoid), tiotropium (a long-acting muscarinic antagonist [LAMA]), or placebo for 12 weeks each, with subsequent crossover through the two remaining treatments. The primary outcome was the response to each active agent, compared with placebo among low-eosinophil patients who had a differential response to a trial agent.
Out of 295 patients, 221 (75%) had low eosinophils and 74 (25%) had high eosinophils. In the low-eosinophil subgroup, 59% of patients had a differential response to a trial agent; among these, 57% responded better to mometasone, compared with 43% who responded better to placebo, and 60% responded better to tiotropium, compared with 40% who responded better to placebo.
Turning to secondary analyses, among patients with high eosinophil levels who had a differential response, 74% responded better to mometasone, compared with 26% who responded better to placebo, and 57% responded better to tiotropium, compared with 43% who responded better to placebo.
In an additional exploratory analysis, adults with low eosinophil levels had better responses to tiotropium than placebo (62% vs 38%).
The researchers stated that a key finding of the study is that three-quarters of the mild, persistent asthma population had low eosinophil levels, far fewer than expected and that the difference in their response to mometasone compared to tiotropium was not significant.
“Our results raise the question of whether treatment guidelines should be reevaluated for patients with mild, persistent asthma for whom evidence of type 2 inflammation is lacking,” the investigators wrote. “The need for a change in treatment strategy is further highlighted by a growing body of literature suggesting that mild, persistent asthma can be managed safely without the daily use of inhaled glucocorticoids and by data showing that patients with a low eosinophil level may not have a favorable response to inhaled glucocorticoids” (New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1814917).
The second study, Novel START, conducted by lead author Richard Beasley, DSc, of the Medical Research Institute of New Zealand, Wellington, and colleagues, compared the efficacy of two inhaled glucocorticoid regimens and albuterol alone for patients with mild persistent or intermittent asthma, measured by annualized exacerbation rate.
Initial randomization involved 675 patients, of whom 668 were included in the final analysis. Patients were randomized into three groups: albuterol as needed (100 mcg, two inhalations as needed for asthma symptoms), budesonide maintenance (200 mcg, one inhalation twice daily with as-needed albuterol), or budesonide/formoterol (budesonide 200 mcg and formoterol 6 mcg, one inhalation as needed). Along with annualized exacerbation rate, several secondary outcomes assessed symptoms, respiratory function, and number of severe exacerbations.
Data analysis showed that patients in the budesonide groups had similar rates of annualized exacerbation, both of which were significantly better than the exacerbation rate in the albuterol-only group; the absolute rate of exacerbations per patient per year was 0.175, 0.195, and 0.400 for budesonide maintenance, budesonide/formoterol, and albuterol only, respectively. Similarly, the median fraction of exhaled nitric oxide (FENO) was lower in the budesonide groups than in the albuterol-only group. Patients in the budesonide/formoterol group had a 56% lower relative risk of severe pulmonary exacerbation than patients in the budesonide maintenance group and a 60% lower relative risk than the albuterol group. However, maintenance budesonide provided better symptom relief than budesonide/formoterol, “which suggests that for the patient for whom asthma symptoms rather than exacerbations are the most bothersome, maintenance treatment has value,” the investigators wrote (New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1901963).
“The findings of our trial are consistent with evidence regarding the treatment of moderate and severe asthma – that maintenance and reliever therapy” with inhaled glucocorticoid/formoterol “results in a lower risk of severe exacerbations than maintenance therapy with an inhaled glucocorticoid–[long-acting beta agonist] and as-needed SABA,” the investigators concluded.
SIENA was funded by National Heart, Lung, and Blood Institute, with medications provided by Boehringer Ingelheim, Merck, and Teva; the investigators reported relationships with Sanofi, Vectura, Circassia, DBV Technologies, and others. Novel START was funded by AstraZeneca and the Health Research Council of New Zealand; the investigators reported relationships with GlaxoSmithKline, Genentech, Theravance Biopharma, and others.
SOURCES: Beasley et al. New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1901963; Lazarus et al. New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1814917.
FROM ATS 2019
Key clinical point: Inhaled glucocorticoid/formoterol therapy for mild persistent or intermittent asthma is effective, but responses to steroids differ among patients with high versus low levels of eosinophils in sputum.
Major finding: Among patients with low eosinophils levels of, 57% responded better to mometasone versus 43% who responded better to placebo. Among those with high eosinophil levels, 74% responded better to mometasone versus 26% who responded better to placebo.
Study details: The SIENA study included 295 patients with mild, persistent asthma and eosinophils measured in sputum samples, and the Novel START study included 688 patients with the mild persistent or intermittent asthma, measured by annualized exacerbation rate.
Disclosures: SIENA was funded by National Heart, Lung, and Blood Institute, with medications provided by Boehringer Ingelheim, Merck, and Teva; the investigators reported relationships with Sanofi, Vectura, Circassia, DBV Technologies, and others. Novel START was funded by AstraZeneca and the Health Research Council of New Zealand; the investigators reported relationships with GlaxoSmithKline, Genentech, Theravance Biopharma, and others.
Sources: Beasley et al. New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1901963; Lazarus et al. New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1814917.